Evidence map›Paper›PMID 42043895›Full record

ArticleMolecular genetics & genomic medicine2026

Confirmation of Exome Sequencing Results Using Sanger Sequencing-Considerations in a Low-Resource Setting.

Nadja Louw, Samantha Schnell, Mhlekazi Molatoli, Ingrid Smit, Robyn Kerr, Koen Devriendt, Aimé Lumaka, Amanda Krause, Nadia Carstens, Zané Lombard and 1 more

Abstract read
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In one paragraph

Article in Molecular genetics & genomic medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Nadja LouwDivision of Human Genetics, National Health Laboratory Service, and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Samantha SchnellDivision of Human Genetics, National Health Laboratory Service, and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Mhlekazi MolatoliDivision of Human Genetics, National Health Laboratory Service, and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Ingrid SmitDivision of Human Genetics, National Health Laboratory Service, and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Robyn KerrDivision of Human Genetics, National Health Laboratory Service, and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Koen DevriendtCenter for Human Genetics, University Hospitals, University of Leuven, Leuven, Belgium.
Aimé LumakaCenter for Human Genetics, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo.
Amanda KrauseDivision of Human Genetics, National Health Laboratory Service, and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.ORCID https://orcid.org/0000-0002-7157-0807
Nadia CarstensDivision of Human Genetics, National Health Laboratory Service, and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.ORCID https://orcid.org/0000-0003-4754-7030
Zané LombardDivision of Human Genetics, National Health Laboratory Service, and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
for DDD‐Africa as members of the H3Africa Consortium

Funding

Deciphering Developmental Disorders in Africa (DDD-Africa) - Evaluating Clinical Exome Sequencing in an African SettingU01MH115483 · NIMH · WITS HEALTH CONSORTIUM (PTY), LTD · PI LOMBARD, ZANE · 2017 to 2021
$1.3M
NIH HHS 5U01HD114537NIMH NIH HHS U01MH115483
6 · The paper itself

Abstract

backgroundExome sequencing (ES) is now widely accepted as an appropriate first-tier diagnostic test for developmental disorders (DD). International guidelines recommend that in diagnostic settings, ES findings be validated with an orthogonal method, such as Sanger sequencing, before reporting. However, more recent guidance recognizes that confirmatory testing for variants meeting strict quality criteria is redundant. Weighing up the cost to benefit ratio of this practice is crucial in settings where ES is not routinely implemented. The Deciphering Developmental Disorders in Africa (DDD-Africa) study aims to enable equitable implementation of genomic medicine in low-resourced settings, focusing on using ES in resolving DD in Africa.

methodsWe performed confirmatory Sanger sequencing for the first 64 probands (70 variants) that underwent ES in which a variant of interest was identified. Strict quality parameters were key to diminishing the observation of false-positive variants.

resultsAll high confidence variants identified by ES (n = 38) were confirmed using Sanger sequencing and low confidence variants (n = 32) were confirmed as false-positive.

conclusionConfirming ES results with an orthogonal approach like Sanger sequencing is unnecessary in a resource-limited setting when robust, context-informed quality thresholds are applied. This recommendation removes significant barriers to the implementation of genomic medicine and allows for accelerated genomic access globally.

Indexed as

Developmental DisabilitiesExome SequencingGenetic TestingSequence Analysis, DNAExomeHumansResource-Limited Settingsexome sequencinggenomic medicineNGS quality metricsresource‐limited settingssanger sequencingvariant confirmation

Identifiers

PMID42043895
PMCPMC13117208

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.